Resolvin E1 attenuates injury-induced vascular neointimal formation by inhibition of inflammatory responses and vascular smooth muscle cell migration.

Mechanical insults, such as stent implantation, can induce endothelial injury, vascular inflammation, and ultimately lead to vascular neointimal hyperplasia. Resolvin E1 (RvE1), derived from the ω3 fatty acid eicosapentaenoic acid, can facilitate the resolution of inflammation in many settings. We therefore aimed to determine if there was a role for RvE1 in preventing neointimal formation after arterial injury and to understand the underlying mechanisms. Vascular inflammation and neointimal hyperplasia were induced by wire injury in the femoral arteries of mice. Administration of exogenous RvE1 and endogenously generated RvE1 via dietary supplementation with eicosapentaenoic acid and aspirin markedly reduced vascular neointima formation in this model. Mechanistically, RvE1 was found to inhibit vascular neutrophil infiltration, promote macrophage polarization toward an M2-like phenotype, suppress T-cell trafficking by reducing RANTES secretion from vascular smooth muscle cells, and inhibit vascular smooth muscle cell migration. In summary, RvE1 demonstrated a protective role against vascular inflammation and remodeling in response to mechanical injury, suggesting that it may serve as an adjuvant therapeutic agent for percutaneous coronary interventions, such as stent implantation.-Liu, G., Gong, Y., Zhang, R., Piao, L., Li, X., Liu, Q., Yan, S., Shen, Y., Guo, S., Zhu, M., Yin, H., Funk, C. D., Zhang, J., Yu, Y. Resolvin E1 attenuates injury-induced vascular neointimal formation by inhibition of inflammatory responses and vascular smooth muscle cell migration.